2. Academic Validation
  3. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M

Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M

  • Blood. 2009 Jul 2;114(1):174-80. doi: 10.1182/blood-2009-02-207811.
Thiyam Ramsing Singh 1,  Sietske T Bakker,  Sheba Agarwal,  Michael Jansen,  Elke Grassman,  Barbara C Godthelp,  Abdullah Mahmood Ali,  Chang-hu Du,  Martin A Rooimans,  Qiang Fan,  Kebola Wahengbam,  Jurgen Steltenpool,  Paul R Andreassen,  David A Williams,  Hans Joenje,  Johan P de Winter,  Amom Ruhikanta Meetei
Affiliations

Affiliation

  • 1 Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
PMID: 19423727 DOI: 10.1182/blood-2009-02-207811
Abstract

FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a "clean" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in Other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the Topoisomerase Inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.

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